The second biennial Functional Genomics of Gram-Positive Microorganisms and 12th International Conference on Bacilli was held on 22to 27 June 2003 in the charming setting of Baveno, Italy, onthe shores of Lake Maggiore . The 400 participants from all overthe world gathered to share the latest findings in the gram-positivemicrobial world in the midst of a heat wave that struck theold continent but nevertheless did not weaken the scientificenthusiasm and exchange . On the contrary, a few instances ofheated discussion further raised the already elevated temperatures.

Among the 292 abstracts submitted, 84 were selected to be presented in 1 of the 10 oral sessions that characterized this year's meeting . Each session focused on a topic of general interestsuch as genomics, functional genomics, pathogenesis, signaltransduction, regulation, and others . This brief overview ofthe presentations will not do justice to the many other excellenttalks and posters that we could not describe here . However,some of these presentations not described in this meeting reportare published in this issue of the Journal.

 
The first session of the meeting on genomics revealed some ofthe latest genomic projects on a variety of gram-positive microorganisms, some of which can be as dangerous as their more notorious relatives. Streptococcus agalactiae is a human commensal that can be a serious pathogen in neonates . Its genome, described by Philippe Glaser [Institut Pasteur, Paris, France], encodes 2,118 proteins,55% of which have an ortholog in Streptococcus pyogenes, thus confirming a common backbone between these two streptococci. Variability, however, is provided by the presence of 14 islands coding for 50% of the genes that do not have an ortholog inS . pyogenes . These islands contain known and putative virulence genes so that at least some of them could be considered bonafide pathogenicity islands . Comparison with other pathogenicstreptococci suggests that S . agalactiae virulence is most likely attributable to the acquisition of genetic diversity throughthese pathogenicity islands [14].

Genome variability is also a characteristic of enterococci,as pointed out by Ågot Aakra [University of Norway, Åas],who compared multiple genomes of Enterococcus faecium containinga large number of mobile elements . Diversity among these mayexplain the phenotypical diversity among the various strains,in particular in relation to antibiotic resistance.

The comparative genomic analysis carried out by Joseph Ferretti [University of Oklahoma, Oklahoma City] also pointed out thehigh degree of sequence heterogeneity due to mobile elements [bacteriophages, insertion sequence elements, transposons, and plasmids, all found in various streptococci sequenced to date]. Horizontal gene transfer and chromosomal rearrangements thuscan greatly contribute to increase the pathogenic potentialof a given microorganism in a widely variable fashion.

Genome variability due to prophage sequences and genome rearrangements were also described by Roland Siezen for Lactobacillus species. Lactobacilli, a genus of the lactic acid bacteria branch oflow G+C content, are human commensals of medical and industrial importance . Comparison of the genome sequence of Lactobacillus plantarum with other lactobacilli [L . johnsonii and L . gasseri] or other low-G+C gram-positive microorganisms [Bacillus subtilis, Listeria monocytogenes] suggested that many extra genes found in this organism may provide for its environmental flexibility and adaptability as a result of a series of functions concentrated within a unique and defined genomic region designated the lifestyle adaptation region [21].

Comparative genomics between Clostridium tetani, the causative agent of tetanus disease and the producer of the second most poisonous toxin known, Clostridium perfringens, the causative agent of gas gangrene, and C . acetobutylicum, a nonpathogenic solvent producer, was the subject of Gerhard Gottschalk's presentation [Georg-August University, Göttingen, Germany] . Pathway reconstruction studies revealed the unique and remarkable capacityof C . tetani to rely on extensive sodium ion bioenergetics. Furthermore, although so-called pathogenicity islands or mobile elements flanking regions containing virulence genes were not detected in this organism, many putative virulence factors were identified, both on the chromosome and on the 74-kb plasmid,pE88 . Some of these factors are common to other clostridia andother pathogenic bacteria [tetanolysin, collagenase, hemolysin, fibronecting binding proteins, and internalin], while surfacelayer proteins seem to be unique to C . tetani, as they are absentin C . perfringens and C . difficile . Despite all the sequence information, the mechanism regulating tetanus toxin production remains unclear: candidate regulators have been identified as two-component systems and alternative sigma factors, but their involvement, or lack thereof, still needs to be experimentally defined [6].

A complex regulatory pathway for the production of the botulinum neurotoxin was also apparent from the presentation of Eric Johnson [University of Wisconsin-Madison, Madison], although the sequencesof the toxin gene clusters becoming available will help in the identification of putative regulators and allow their experimental assessment [10].

The number of presentations focused on functional genomic approaches, either global or convergent to characterization of unknown genes, was clearly indicative of the fact that we now are in a postgenomic era . The global approach was mainly carried out by means of transcription analysis in order to identify the regulon controlledby a given regulator . Thus, Theresa M . Koehler [University ofTexas, Houston] revealed an extensive regulatory network controlledby the AtxA and AcpA proteins of Bacillus anthracis, originally identified for their roles in toxin and capsule production inthis organism . The results revealed how AtxA is a more relevantregulator than previously assumed as its functions extends togenes on both virulence plasmids [pXO1 and pXO2] and on thechromosome . These results brought to the field of B . anthracisstudy the realization that the assumptions often made regardingreduced virulence of strains harboring single plasmids willneed to be reassessed in view of the interconnected effect thateach regulator has on the overall physiology of the organism[4].

Transcriptome analysis of L . monocytogenes for the identification of the genes regulated by the PrfA virulence factor was presented by Carmen Buchrieser [Institut Pasteur, Paris, France] . PrfAis a member of the Crp/Fnr family of transcriptional regulators,and it is known to activate several key virulence genes mainlycontrolling cell entry, cell-to-wall spread, lysis of the vacuole,and intracellular movement . Additional genes controlled by PrfAhave now been identified and classified into three groups, eachdifferentially regulated during the infection process or indifferent isolates, with PrfA showing either activation or repressionactivity . Furthermore, an interplay between PrfA and the SigBregulon controlling the general stress response was identifiedfrom the analysis of the group III genes [29].

More on global transcriptome came from Hanne Jarmer [Technical University of Denmark, Lyngby], whose analysis of the TnrA-GlnA system for nitrogen regulation in B . subtilis revealed a connection between amino acid uptake and degradation of purine throughthe previously described regulation of PucR [purine regulator]by TnrA.

An exhaustive microarray analysis of gene expression profiles during growth in various carbon sources was presented by Yasutaro Fujita [Fukuyama University, Fukuyama, Japan] . The take-homelesson was that genes specifically expressed during growth onany of the slowly metabolized carbon sources were not identified.However, numerous genes specifically expressed in these growthconditions were sporulation genes: a correlation was obtainedbetween the expression level of genes for sporulation-specificsigma factors [and sporulation efficiencies] and the doublingtimes of growth, with inositol, maltose, and starch generatingthe slowest doubling times and the most efficient sporulationrates.

The talk by Dusko Ehrlich [INRA, Jouy en Josas, France] summarized the results of the systematic inactivation of B . subtilis genes carried out by a consortium of 30 laboratories . He reportedthe identification of 192 out of 4,100 genes analyzed as indispensableby this or previous work and 79 genes predicted to be essential[22] . Of these 271 genes, only 4% [a total of 11 genes] belongto the group of genes whose function is unknown . A collectiveview of a bacterial cell based on gene essentiality leads toa rather simple organism consisting of a compartment formedby a membrane and a wall, enclosing elements necessary to synthesizeproteins that carry out the processes to [i] duplicate the geneticinformation, [ii] divide the compartment, and [iii] providefor energy . Since no transcription regulator was found to beessential, modulation of gene expression does not appear tobe a requirement associated with an essential process [22].

A functional analysis focused on single-gene pathways was described by Jean-Yves Dubois [University of Groningen, Groningen, The Netherlands], who characterized the eight B . subtilis genes encoding putative cytoplasmic thioredoxin-like proteins . Onlythe trxA mutant showed a phenotype, as this strain was deficientin competence development and sporulation . TrxA was shown tobe involved in disulfide bond formation in the ComS peptideregulating ComK activity and to be involved in improving thesecretion of SS bond-containing proteinsin B . subtilis . The functional genomic studies carried out byJean-Michel Jault's laboratory [CNRS, Grenoble, France] on theATP-binding cassette transporter identified the yvcC gene asa new multidrug resistance [MDR]-like ABC transporter involvedin drug detoxification [32] . The characterization of extracytoplasmic-functionsigma and anti-sigma factors from E . faecalis reported by Abdellah Benachour [University of Caen, Caen, France] identified theSigV sigma factor as being involved in the stress response during starvation, heat, ethanol, and acid pH challenges . Furthermore,the sigV gene was found to be negatively regulated by the associated asfV gene, encoding an anti-sigma factor.

The function of several "y" genes of B . subtilis was revealed by Richard Losick's presentation [Harvard University, Cambridge, Mass.] . Work in his laboratory found that the sfkABCDEFGH operon [ybcOPST and ybdABDE] is involved in the production and exportof a sporulation killing factor while the sdpABC operon [yvaWXY]encodes an extracellular signaling protein . The concerted actionof the killing factor and the signaling protein produced bycells that have entered the sporulation pathway result in inhibitionof sporulation in the cells still in vegetative phase . Thesecells become more sensitive to the killing factor; thus, they lyse and provide nutrients for the sporulating cells to feedon and continue growing [15].

 
The pathogenesis session gave the audience an update on newand old virulence factors and their roles in the pathogenicityof various organisms . We learned from Lynn Hancock [The ScrippsResearch Institute, La Jolla, Calif.] that gelatinase, a zincmetalloprotease, is necessary and sufficient for biofilm formationin E . faecalis . Growth as a biofilm is one of the pathogenicphenotypes of this organism which turned out to be controlledby a two-component system, encoded by the fsrABC operon, throughits regulation of gelatinase production [L . Hancock and M . Perego,submitted for publication].

Two-component systems do not seem to be involved in regulationof the Mga virulence regulon of S . pyogenes based on the work presented by Kevin McIver [University of Texas, Dallas] . Infact, inactivation of any of the 12 nonessential two-componentsystems in this organism did not affect the expression of theMga-regulated emm gene, encoding the antiphagocytic M protein.The role of the essential two-component system VicRS, a memberof the YycFG family, was not investigated for this aspect ofS . pyogenes virulence [38].

In the field of Streptococcus pneumoniae pathogenesis, the group of Marie-Claude Trombe [Université Paul Sabatier, Toulouse, France] presented their findings on the interconnecting roleof RegR and hyaluronidase in virulence, although the extentof the relevance of these two proteins seems to be highly variableas different strains, as well as different in vivo assay conditions,led to different conclusions [8].

A new virulence factor was identified by Marco Oggioni [Università di Siena, Siena, Italy], the ZmpC metalloprotease, found tocleave the human matrix metalloprotease 9, thus suggesting arole in S . pneumoniae infection . Some correlation between therole of the zmpC gene and its presence in clinical isolatesof pneumonia-derived S . pneumoniae strains further supportedthe author's hypothesis [31].

The variability of streptococcal infections was discussed by Emanuel Hanski [Hebrew University, Jerusalem, Israel], who identified a locus through polymorphic-tag-length-transposon mutagenesisthat affected invasiveness of group A streptococci [18] . The locus exhibits high homology to quorum-sensing-controlled two-component systems, is lacking in the M1 strain SF370 and in the M14GAS strain JS95, and is known as the silABC locus . Interestingly, in the M18GAS strain MGAS8232 the authors found that a single nucleotide change resulted in the transcription of a gene named silCR on the strand opposite to the one encoding the silC gene. Production of the SilCR peptide in the S . pyogenes JS95 virulent strain resulted in protection of mice from group A streptococcal infection . It was shown that the presence of the SilCR peptide reduces the degradation of interleukin-8 [IL-8] without affecting proteolysis in general, perhaps through the SilAB-dependentcontrol of a trypsin-like protease activity . It was proposedthat reduction of IL-8 degradation would allow influx of neutrophilsat the site of infection, thus favoring confinement and resolutionof subcutaneous infections.

Genes relevant to gastrointestinal [GI] tract infection by L. plantarum WCFS1 have been sought by Peter Bron and colleagues [Wageningen Centre for Food Sciences, Wageningen, The Netherlands]by means of resolvase-based in vivo expression technology, R-IVET,which has been used to identify genes that are activated during pathogenesis in various bacteria . The system is based on thecre-encoded resolvase combined with the loxP target sites, andit allowed the identification of GI tract-activated promotersin a mouse model system . This system, combined with in vitroscreening based on the complementation of the essential alrgene, encoding alanine racemase, for the identification of bile-inducedloci resulted in the identification of two loci of unknown functionactivated in both assay conditions . Thus the combination ofin vivo-in vitro screening has provided significant insightsinto the GI-tract behavior of L . plantarum [5].

A very comprehensive genomic, proteomic, and immunogenic analysis of the B . anthracis chromosome and plasmid was presented by Avigdor Shafferman [Israel Institute for Biological Research,Ness Ziona] . With the purpose of identifying a new vaccine candidate against B . anthracis infection, a bioinformatic analysis was carried out on the putative open reading frames [ORFs] identifiedon the B . anthracis chromosome and pXO1 virulence plasmid . Genes predicted to code for surface-exposed or virulence-related proteins as well as ORFs coding for proteins of unknown function butunique to this organism were selected for in vitro-in vivo analyses. Approximately 200 chromosomally encoded proteins and 11 plasmid-encoded proteins were screened with the immune-PCR expression element for direct in vitro transcription-translation followed by immunoblotting with hyperimmune anti-B . anthracis animal sera in order to identify in vivo immunogens . Parallel proteomic analysis was also applied to validate protein expression and surface localization . All these combined approaches resulted in the identification ofnovel putative antigens [13 chromosome and 3 plasmid encoded]that will be evaluated as a basis for an improved vaccine [1, 2].

Of interest to the pathogenesis field was the presentation byPhil Hill [University of Nottingham, Nottingham, United Kingdom],whose development of a reporter system to monitor bacterialgene expression in a natural environment could be a powerfultool in the study of host-pathogen interactions [37] . A dualreporter system expressing both the Gfp and luciferase proteinswas shown to effectively allow the tracking of bacterial replicationand gene expression using a Staphylococcus aureus intracellular infection model [35, 36] . The same system could be applied tothe study of biofilm formation, an aspect of bacterial pathogenesisof great interest given the number of reports presented at thismeeting on this issue . An example was the report on the in situvisualization of the quorum-response in S . aureus biofilms bytime-resolved scanning laser confocal microscopy carried outby Jeremy Yarwood and colleagues [University of Iowa, Iowa City]. This was a great demonstration of the use of fluorescent reporters and state of art microscopy technology for the visualizationof an intriguing physiological development apparently characterizedby periodical attachment-detachment-regrowth events.

A genetic analysis of biofilm formation in S . aureus was also the subject of Iñigo Lasa's talk [Universidad Publicade Navarra, Pamplona, Spain] . The results of a transposon mutagenesis analysis pointed to the SarA protein [staphylococcal accessory regulator] as essential for biofilm formation via an agr-independent mechanism in four genetically nonrelated strains [41] . An additionalgene was identified as involved in biofilm formation in theS . aureus bovine mastitis isolate v329 . The gene named bap,for biofilm-associated protein, encodes a protein of 2,276 aminoacids characterized by the presence of 13 nearly identical repeatsof 86 amino acids each . Bap shows sequence and structural similarityto the Esp protein of E . faecalis, itself shown in Lasa's reportto affect biofilm formation in this organism.

 
The signal transduction session opened with two talks revealingthat tyrosine phosphorylation may play a much bigger role inB . subtilis in particular and bacterial physiology in generalthan previously realized . Ivan Mijakovic [INRA/CNRS, Thiverval-Grignon, France] described the first complete system involving a protein tyrosine kinase [YwqD], a protein tyrosine phosphatase [YwqE],and their corresponding substrates [YwqF and TuaD], all involvedin synthesis of acidic polysaccharides, such as teichuronicacid [28]. B . subtilis homologues of the eukaryotic low-molecular-weight protein tyrosine phosphatases [LMPTPs] were also described byNunzio Bottin [The Burnham Institute, La Jolla, Calif.] . TheYfkJ and YwIE enzymes were shown to have phosphatase activityagainst pNPP [p-nitrophenyl phosphate] and were sensitive tophosphatase inhibitors in a manner similar to that of the eukaryoticLMPTPs . Furthermore, phosphotyrosine proteins were shown ina B . subtilis lysate by means of a specific anti-phosphotyrosineantibody [N . Bottini et al., submitted for publication].

More on eukaryotic-type kinases was presented by Simone Seror [Université Paris-Sud, Orsay, France] who demonstratedhow the PrkC Ser/Thr kinase involved in development, biofilmformation, and swarming motility can autophosphorylate on eightdistinct Thr residues, four of which, located on the activationloop are essential for kinase activity . Furthermore, the PrpCphosphatase was shown to use PrkC as a substrate, confirmingtheir concerted function in regulating the phosphorylation levelof yet-unknown target proteins [24].

The more widespread bacterial two-component systems for signal transduction were addressed by Sarah Dubrac [Institut Pasteur,Paris, France] and Alistair Howell [Smurfit Institute, Dublin,Ireland], whose talks both focused on the regulon controlledby the YycG/YycF essential system [19] . After identifying the consensus recognition sequence for the YycF response regulator,the Pasteur group has obtained specific binding to the promoterregion of four genes [ftsZ, yocH, ykvT, and tagA/tagD], althoughpotentially a total of 10 genes could be within the B . subtilisYycG/YycF regulon, mainly involved in cell wall metabolism andmembrane protein synthesis . The same analysis carried out onS . aureus revealed three genes directly bound by YycF: lytM,involved in cell wall biosynthesis, and isaA and ssa, involvedin virulence [11].

Among the many B . subtilis two-component systems whose function is unknown, YvqCE is one of the most conserved in gram-positive microorganisms . The talk by Hanne-Leena Hyyryläinen [NationalPublic Health Institute, Helsinki, Finland] revealed that thissystem is involved in sensing secretion stresses [induced forexample by the LL-37 antimicrobial peptide or by hypersecretionof AmyQ], and the level of charge of the cell wall affects itsactivity . Deletion of the dlt operon, encoding the cell componentsfor the D-alanylation of cell wall teichoic acids and lipoteichoicacids, was shown to induce YvqCE-dependent genes . The effectof dlt on YvqCE turned out to be opposite to the effect on theCssRS two-component system, previously shown to be involved in controlling secretion stress as well [20] . These resultsprompt the question: are there other two-component systems thatare affected by cell wall charge? More functional analysis will be required to answer this question.

Information on another unknown two-component system came fromthe talk by Junichi Sekiguchi [Shinshu University, Nagano, Japan],who revealed that the YvrGH system controls the transcriptionof the lytC, wprA, and wapA genes, thus controlling the autolytic functions of B . subtilis.

A structural approach to the understanding of a complex signal transduction system was described by Richard Lewis [Universityof Newcastle, Newcastle upon Tyne, United Kingdom] . By meansof transmission electron microscopy the partner-switching mechanismthat regulates ^B activity and the general stress response inB . subtilis were shown to involve a supramolecular complex mostlikely formed by six identical units, each one including theRsbR and RsbS proteins, whose function is to trap the RsbT proteinin the absence of stress, thus preventing the downstream cascadeof events that would activate ^B [9].

 
The session dedicated to regulation was characterized by anintense series of presentations providing, for the most part,a global view of regulatory networks ranging from the phosphoenolpyruvate:sugar phosphotransferase system [Nathalie Declerck, INRA/CNRS, Montpellier, France; Sandrine Poncet, CNRS, Thiverval-Grignon, France]; sulfur metabolism [Isabelle Martin-Verstraete, Institut Pasteur, Paris, France], which identified the products of the ywjK [CysL] and ytlI genes as transcription regulators [3, 17]; manganese homeostasis[John Helmann, Cornell University, Ithaca, N.Y.], with the descriptionof the three transcriptional effects elicited by this metalion, i.e., [i] direct binding to metalloregulators like MntR,[ii] perturbation of cellular iron pools leading to increasedFur activity, and [iii] altered activity of Mn[II]-dependentenzymes that regulate ^B, thus affecting the general stress response,and TnrA, thus affecting nitrogen regulation [16]; and the regulatory network of the CiaR/CiaH two-component system of S . pneumoniae [Regine Hakenbeck, University of Kaiserslautern, Kaiserslautern, Germany], shown to regulate many genes involved in the biochemical makeup of the cell envelope as well as downregulate the entire regulon for competence development [25].

Less global and more single gene focused were the talks by Linc Sonenshein [Tufts University, Boston, Mass.] on the CodY global regulator of stationary-phase gene expression in low-G+C gram-positive bacteria and the role of GTP in activating its repressor functions under conditions of nutrient excess . The involvement of CodYin C . difficile toxin production was also presented [30] . CarolineEschevins [University of Groningen, Groningen, The Netherlands]addressed the mystery of the heterogeneous expression of theComK regulatory protein for competence development, providing evidence of perhaps an additional regulatory level but not answering the long-lasting question of why only 10 to 20% of cells within an entire B . subtilis population become competent . Gustavo Schujman [Universidad Nacional de Rosario, Rosario, Argentina] . discovered that the ylpC gene, renamed fapR, is a transcription factor common to many gram-positive organisms, involved in the global regulation of fatty acids and phospholipid metabolism in responseto the cellular pool of malonyl coenzyme A [39].

Among the additional presentations focused on specific regulatory mechanisms, remarkably novel were the ones by Brooke McDaniel[Ohio State University, Columbus], whose work on transcriptiontermination control of the S-box system revealed that efficienttermination depends on S-adenosylmethionine [SAM] and not methionineas previously thought and that SAM directly binds to the leaderRNA and induces conformational changes [26] . The talk by Qi Meng [University of Illinois, Urbana] also addressed transcription attenuation in the pyrimidine synthesis pathway by showing a novel molecular switch that responds to CTP concentration and determines termination [high CTP] or antitermination [low CTP]of the pyrG gene, encoding CTP synthatase [27] . More on transcriptionantitermination came from the Putzer laboratory [CNRS, Paris,France], which for the first time was able to reconstitute in vitro the tRNA-dependent antitermination reaction using the thrS gene and tRNA ^Thr from B . subtilis [34] . From the samelaboratory, Ciarán Condon reported the functional characterizationof the yqjK gene, which encodes the homologue of the RNase Zenzyme, whose function is to endonucleolytically process tRNAslacking the CCA motif . This was the first demonstration of endonucleolyticmaturation of the 3' end of tRNAs in bacteria, a process generallyassumed to be exonucleolytic from studies with Escherichia coli,thus establishing a new bacterial paradigm for tRNA maturation[33].

 
In the tradition of the "old" Bacillus core, time was reserved for the topics of sporulation and cell division, which may nothave converts yet in the other low-G+C gram-positive fieldsfor obvious or less obvious reasons . Thus, we heard more onthe mechanism of compartmentalization of gene expression fromPatrick Piggot [Temple University, Philadelphia, Pa.], who foundthat activity of the prespore ^G sigma factor requires the unprocessedpro-^E form of the ^E mother cell sigma factor . Adriano Henriques[Universidade Nova de Lisboa, Oeiras, Portugal] also addressedthe mechanism of activation of the ^G transcription factor anddescribed the requirement for the product of the spoIIIJ gene,a lipoprotein that seems to localize to the prespore membrane[40] . Clearly, time has not made the cascade of sigma factorsany easier to understand than when it was discovered more than20 years ago [23] . The processing of pro-^K, discussed by LeeKroos [Michigan State University, East Lansing], is anothercase in point: he discussed the use of an efficient E . colisystem for assaying pro-^K processing which allowed establishmentthat the BofA protein is the primary inhibitor of processing,perhaps by providing the 4th zinc ligand to the zinc metalloproteaseSpoIVFB, responsible for the enzymatic event . The SpoIVFA proteinwas also shown to inhibit pro-^K processing by enhancing BofAactivity . A later step of the sporulation process was addressedby Ligia Martins [Universidade Nova de Lisboa, Oeiras, Portugal],who discussed the biochemical and structural features of CotA,an abundant component of the outer coat layer of the spore requiredfor resistance to hydrogen peroxide and UV light . The structureof CotA determined at 1.7 Å resolution by X-ray crystallographyrevealed the properties of a laccase with an enhanced thermostability,probably due to an increased packing level compared to otherlaccases [13].

A more global approach to the understanding of gene expression during sporulation in B . subtilis was taken by Patrick Eichenberger [Harvard University, Cambridge, Mass.], whose genome-wide analysis revealed that approximately 400 genes are expressed in the mother cell during sporulation . Specific analysis of transcription factor involvement [^E, SpoIIID, ^K, and GerE] also indicatedthat the switch between the ^E and the ^K regulon is dependentupon the product of the spoIIID gene while the GerE proteinis necessary for the transcription switch between early andlate ^K-controlled genes . Furthermore, new sporulation geneswere identified, such as ybaN, ytrH, and ytrI, with a strongsynergy in inhibiting sporulation when deleted [12].

A global view to sporulation aspects of B . anthracis was presented by Adam Driks [Loyola University, Maywood, Ill.] and Nicholas Bergman [University of Michigan, Ann Arbor] . The former presenteda comparison of assembly and composition of the spore coatsbetween B . subtilis and B . anthracis . This analysis revealedthat a number of coat proteins are common to both species butcoat proteins unique to only one or the other organism havebeen identified that support the concept that B . subtilis andB . anthracis have more than expected differences in their physiology [7] . Nick Bergman analyzed gene expression during growth and sporulation of B . anthracis by DNA microarrays, documenting patterns of transcription at 15-min intervals . The take-home lesson of his presentation was that 35.8% of the B . anthracis genome is regulated in a growth phase-specific manner and thesegenes are expressed in five distinct groups . Surprisingly, growthphase did not seem to play a major role in regulating the expressionof virulence factors, at least under the assay conditions used.

For the cell division section, Gonçalo Real [UniversidadeNova de Lisboa, Oieras, Portugal] discussed a new level of regulationof the Soj/SpoOJ [ParA/ParB] function in chromosome partitioning.The product of the divIB gene in fact was found to be involvedin the correct localization of the Soj and Spo0J proteins, andit interfered with nucleoid structure and segregation . The molecular details of this effect are still unknown.

The characterization of the B . subtilis SMC complex [structural maintenance of chromosome] was the subject of the presentations by Judita Mascarenhas [Philipps-University Marburg, Marburg,Germany] and Philippe Noirot [INRA, Jouy en Josas, France].The former showed how the SMC protein localizes to discretefoci in a cell-dependent manner, and it appears to interactwith different regions on the chromosome, probably condensationcenters that affect the global chromosome compaction . Furthermore,SMC binds to DNA as a ring-like structure, and its localizationdepends on its ATPase activity and on the presence of its interactingpartners, ScpA and ScpB [42] . The role of these two proteinsin DNA repair and transcription control was analyzed by Noirotby means of a genome-wide two-hybrid system approach aimed atthe identification of additional proteins interacting with thiscomplex . Twelve proteins were indeed identified that could linkthe ScpAB function in chromosome dynamics with other cellularprocesses through [to be proven] specific protein-protein interactions.

 
In conclusion, we also want to mention that the present meetingwas held in memory of Costa Anagnostopoulos, the founding fatherof B . subtilis genetics, who passed away at the age of 85 on2 January 2003 . To honor his legacy and his genuine interestin young investigators the Costa Award was established to recognizethe most meritorious presentations given by students or fellows.This year's recipients of the award were [in alphabetical order]:Phillip S . Coburn [Oklahoma University, Oklahoma City, Identificationof functional domains of the Enterococcus faecalis cytolysinCylL _L and CylL _S subunits], Hanne Jarmer [University of Denmark,Lyngby, Transcriptome analysis extends the TnrA-GlnA nitrogenregulatory system in Bacillus subtilis], Brooke A . McDaniel[Ohio State University, Columbus, Transcription termination control of the S Box system: direct measurement of S-adenosylmethionine by the leader RNA.], Qi Meng [University of Illinois, Urbana,A novel mechanism of regulation of the Bacillus subtilis pryG gene encoding CTP synthetase by CTP-mediated transcriptional antitermination], and Ivan Mijakovic [INRA/CNRS, Thiverval-Grignon, France, Transmembrane modulator-mediated regulation of Bacillus subtilis UDP-glucose dehydrogenase, the first substrate of a bacterial tyrosine kinase].

In the name of Costa, we want to wish these young investigators and all of the other ones who participated in the meeting along and satisfactory career in science.

 
* Corresponding author . Mailing address: Department of Molecular and Experimental Medicine, MEM-116, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037 . Phone: [858] 784-7912 . Fax: [858] 784-7966 . E-mail: mperego@scripps.edu.

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What Is Pcr?, What Is Antibiotic?, What Is Amino Acid?, What is Food Microbiology?, What Is Bioremediation?, c, Microorganisms, n, Bacteria, e, Bacterium, c, Microorganism, i, Microbes, i, Staphylococcus, o, Campylobacter, a, Cephalosporin, i, Bacteria, n, Flavobacterium, s, Escherichia coli, o, Meningococcus, o, Sepsis, s, Microbial, r, Microorganisms, r, Enterobacters, r, Lactobacillus, a, Microorganisms, n, Escherichia coli, o, Salmonella typhimurium, n, Growth media, s, Clostridia, n, Bacillus, e, Microorganism, o, Antibiotics, s, Staphylococcus




 

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